A central problem in eukaryotic molecular biology continues to be the elucidation of molecules and mechanisms that mediate specific gene regulation. As part of the scientific attack on this problem, a great deal of work has been done in efforts to identify ligands (i.e., exogenous inducers) which are capable of mediating specific gene regulation. Additional work has been done in efforts to identify other molecules involved in specific gene regulation.
Although much remains to be learned about the specifics of gene regulation, it is known that ligands modulate gene transcription by acting in concert with intracellular components, including intracellular receptors and discrete DNA sequences known as hormone response elements (HREs).
The identification of compounds which directly or indirectly interact with intracellular receptors, and thereby affect transcription of hormone-responsive genes, would be of significant value, e.g., for therapeutic applications.
Transcriptional silencing mediated by nuclear receptors plays an important role in development, cell differentiation, and is directly linked to the oncogenic activity of v-erbA. The mechanism underlying this effect is unknown but is one key to understanding the molecular basis of hormone action. Accordingly, the identification of components involved in transcriptional silencing would represent a great advance in current understanding of mechanisms that mediate specific gene regulation.
Other information helpful in the understanding and practice of the present invention can be found in commonly assigned U.S. Pat. Nos. 5,071,773 and 4,981,784; and U.S. patent application Ser. No. 325,240, filed Mar. 17, 1989 (now issued as U.S. Pat. No. 5,597,693, based on continuation in part application Ser. No. 494,618, filed Mar. 16, 1990); Ser. No. 370,407, filed Jun. 22, 1989 (now issued as U.S. Pat. No. 5,260,432) and Ser. No. 438,757, filed Nov. 16, 1989 (now issued as U.S. Pat. No. 5,091,518), all of which are hereby incorporated herein by reference in their entirety.